title: MicroRNA-23a modulates tumor necrosis factor-alpha-induced osteoblasts apoptosis by directly targeting Fas.
abstract: Tumor necrosis factor (TNF)-alpha is a key cytokine regulator of bone and mediates inflammatory bone loss. The molecular signaling that regulates bone loss downstream of TNF-alpha is poorly defined. Recent studies implicated an important role of microRNAs (miRNAs) in TNF-alpha-mediated bone metabolism, including osteoblasts differentiation, osteoclasts differentiation and apoptosis. However, there are very few studies on the complex regulation of miRNAs during TNF-alpha-induced osteoblasts apoptosis. In the present study, the clonal murine osteoblastic cell line, MC3T3-E1, was used. We screened for differentially expressed miRNAs during TNF-alpha induced MC3T3-E1 cell apoptosis and identified microRNA-23a as a potential inhibitor of apoptosis. To delineate the role of microRNA-23a in apoptosis, we respectively silenced and overexpressed microRNA-23a in MC3T3-E1 cells. We found that microRNA-23a depletion significantly enhances TNF-alpha-induced MC3T3-E1 cell apoptosis and over-expressing microRNA-23a remarkably attenuates this phenomenon. Mechanistic studies showed that microRNA-23a inhibits Fas expression through a microRNA-23a-binding site within the 3'-untranslational region of Fas. The post-transcriptional repression of Fas was further confirmed by luciferase reporter assay. These results showed that microRNA-23a, an important protecting factor, plays a significant role in the process of TNF-alpha induced MC3T3-E1 cell apoptosis, by regulating Fas expression.
authors.affiliation: Department of Orthopaedics, Provincial Hospital Affiliated to Shandong University, Jinan, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Dong
authors.forename: Xingang
authors.initials: X
authors.lastname: Cui
authors.forename: Zhensong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Jianmin
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor
keywords: APOPTOSIS; Fas; MC3T3-E1; TNF-alpha; microRNA-23a